title: Oral and craniofacial manifestations and two novel missense mutations of the NTRK1 gene identified in the patient with congenital insensitivity to pain with anhidrosis.
abstract: Congenital insensitivity to pain with anhidrosis (CIPA) is a rare inherited disorder of the peripheral nervous system resulting from mutations in neurotrophic tyrosine kinase receptor 1 gene (NTRK1), which encodes the high-affinity nerve growth factor receptor TRKA. Here, we investigated the oral and craniofacial manifestations of a Chinese patient affected by autosomal-recessive CIPA and identified compound heterozygosity in the NTRK1 gene. The affected boy has multisystemic disorder with lack of reaction to pain stimuli accompanied by self-mutilation behavior, the inability to sweat leading to defective thermoregulation, and mental retardation. Oral and craniofacial manifestations included a large number of missing teeth, nasal malformation, submucous cleft palate, severe soft tissue injuries, dental caries and malocclusion. Histopathological evaluation of the skin sample revealed severe peripheral nerve fiber loss as well as mild loss and absent innervation of sweat glands. Ultrastructural and morphometric studies of a shed tooth revealed dental abnormalities, including hypomineralization, dentin hypoplasia, cementogenesis defects and a dysplastic periodontal ligament. Genetic analysis revealed a compound heterozygosity--c.1561T>C and c.2057G>A in the NTRK1 gene. This report extends the spectrum of NTRK1 mutations observed in patients diagnosed with CIPA and provides additional insight for clinical and molecular diagnosis.
authors.affiliation: Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an, Shaanxi Province, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Gao
authors.forename: Hao
authors.initials: H
authors.lastname: Guo
authors.forename: Nan
authors.initials: N
authors.lastname: Ye
authors.forename: Yudi
authors.initials: Y
authors.lastname: Bai
authors.forename: Xin
authors.initials: X
authors.lastname: Liu
authors.forename: Ping
authors.initials: P
authors.lastname: Yu
authors.forename: Yang
authors.initials: Y
authors.lastname: Xue
authors.forename: Shufang
authors.initials: S
authors.lastname: Ma
authors.forename: Kewen
authors.initials: K
authors.lastname: Wei
authors.forename: Yan
authors.initials: Y
authors.lastname: Jin
authors.forename: Lingying
authors.initials: L
authors.lastname: Wen
authors.forename: Kun
authors.initials: K
authors.lastname: Xuan
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D002648:Child; D017124:Conserved Sequence; D019465:Craniofacial Abnormalities / Q000175:diagnosis* / Q000235:genetics; D004252:DNA Mutational Analysis; D009477:Hereditary Sensory and Autonomic Neuropathies / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D020917:Receptor, trkA / Q000235:genetics*; D014071:Tooth Abnormalities / Q000175:diagnosis* / Q000235:genetics
chemical_list: D020917:Receptor, trkA